Pharmacokinetic studies of mouse monoclonal antibodies to a rat colon carcinoma: I. Comparison of biodistribution in normal rats, syngeneic tumor-bearing rats, or tumor-bearing nude mice

The pharmacokinetics of two iodine-131-(131I) labeled murine anti-rat colon carcinoma monoclonal antibodies (D3 and E4) were compared in normal Sprague Dawley rats, syngeneic BDIX rats, or nude mice bearing that tumor. Results of antibody uptake after i.v. administration were analyzed in terms of accumulation and localization indices for normal tissues and tumor. Statistically significant differences between rat and mouse tissue biodistribution were found. D3, which reacts in vitro with the tumor and several normal rat tissues, cleared quickly from the blood of rats and was specifically targeted to several normal tissues, notably the lung. Virtually no targeting to the tumor was observed. Nude mice, however, showed a slower blood clearance and specific antibody targeting only in the tumor. Similar results were seen after injection of another antibody, E4, which is tumor-specific in vitro. Data suggest that studies on the xenogeneic nude mouse model may not necessarily be relevant to the choice of monoclonal antibodies for clinical diagnostic imaging or therapy.     

Gallbladder volume and contractility in term and preterm neonates: normal values and clinical applications in ultrasonography

The aim of this study was to establish the normal values and evaluate associated factors of gallbladder volume and contractility in term and preterm neonates by using ultrasonography. Sonographic measurement of gallbladder volume was performed by using the ellipsoid method in 50 preterm and 46 term infants. We collected data soon after delivery and at 6-h fasting, and at 3-h and 6-h fasting following regular milk feeding. Serial postprandial changes of gallbladder volume and contractility were collected at 15-min intervals for one hour. Gallbladder contraction index (C.I.) was determined as percentage decrement of postprandial size from initial size. Fasting gallbladder volume was larger in term group ( p < 0:05). Term neonates more readily showed significant contraction (C.I. > 50%; p < 0:05). In preterm infants significant contraction was clearly observed at postconceptional age > 31 weeks or body weight > 1300 g. The presence of hepatobiliary diseases might be detected by evaluating serial changes of gallbladder volume and contractility under ultrasonography in the neonatal stage.     

Bacterial resistance to biocides in the healthcare environment: should it be of genuine concern?

The emergence of bacterial resistance following exposure in healthcare facilities has been a recurrent topic of interest over the last 10 years. The overwhelming and increasing body of evidence from studies in vitro showed that bacteria have an immense capacity to respond to chemical stress brought upon by biocides. Empirically two major types of mechanisms have been described: intrinsic and acquired. However, the increasing documented response from bacteria exposed to biocide in conditions close to those found in practice suggests that intrinsic resistance does not adequately describe bacterial survival mechanisms, and that other terms such as biofilm resistance and environmental resistance would be therefore more appropriate. In addition, such terms are more relevant when describing in-situ conditions. The lack of evidence of bacterial resistance in practice and the inability to correlate emerging bacterial resistance from in-vitro experiments with practical situations is a major drawback when attempting to ascertain whether emerging bacterial resistance in healthcare facilities is of genuine concern. Microbial resistance to high or in-use concentration of biocides has been described in practice, although it remains uncommon. The efficacy of biocides in eliminating bacterial contaminants within healthcare facilities has to be questioned with the widespread and increasing use of products containing low concentrations of biocide or possessing low bactericidal activity, as is the selection of less susceptible bacteria following such exposure.     

Radiation therapy with 131I-MIBG is still relevant for metastatic carcinoid tumors

We report different treatment options (currently used and on trial) for a patient with a gastrointestinal carcinoid tumor and metastases in the liver, and discuss the advantages of using internal radiotherapy with 131I-MIBG rather than other treatments. According to the literature, this pathology has a poor prognosis, and considering the significant efficacy of this radiopharmaceutical treatment on symptoms, tumor reduction, and biochemical parameters, it seems to be under used. There are currently no standard treatment options. We present a management strategy for gastrointestinal carcinoid tumors with 131I-MIBG.     

Relationship between body-mass index and serum folate concentrations in pregnant women

The concentration of micronutrients impacts fetal development and pregnancy outcome and has been suggested to be negatively correlated with the body-mass index (BMI). We evaluated the relationship between BMI and the serum folate concentration in 802 and 660 Korean pregnant women in mid- and late pregnancy, respectively, who participated in a multicenter prospective study. There was a significant negative correlation between BMI value and the serum folate concentration at mid- and late pregnancy (P for trend 0.001 and 0.024, respectively). A general linear model confirmed this correlation at both time points after adjusting for gestational age and total folate intake. These findings are important as the serum folate concentration is a rate-limiting factor for placental folate transport to the fetus, and an inadequate folate supply may cause various malformations.     

Reduction in PINP, a marker of bone metabolism, with raloxifene treatment and its relationship with vertebral fracture risk

In the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, 7705 postmenopausal women with osteoporosis, defined by low bone mineral density and/or prevalent vertebral fractures (VF), were randomized to placebo or raloxifene (60 or 120 mg/day). All women received daily calcium (500 mg) and vitamin D (400-600 IU) supplements. Our previous analyses found that changes in BMD and biochemical markers of bone turnover are poorly predictive of the reduction in VF risk observed with raloxifene. This present study evaluated the effects of raloxifene on type I procollagen N-terminal propeptide (PINP), a new marker of bone turnover. Logistic regression analysis models evaluated the relationships between the changes at 1 year in PINP, serum osteocalcin (OC), bone-specific alkaline phosphatase (BSAP), and urinary excretion of type I collagen C-telopeptide fragments normalized to creatinine (CTx/Cr), and the risk of new VF at 3 years for placebo and pooled raloxifene. A subset of 967 women (mean age = 68 years) from the MORE cohort had PINP, OC, BSAP, and CTx evaluated at baseline. Both doses of raloxifene significantly decreased (P < 0.001) all biochemical markers of bone turnover from baseline. Compared to baseline, PINP levels were decreased by medians of 11.0% and 40.8% in the placebo and pooled raloxifene groups, respectively. In addition, the placebo and pooled raloxifene groups decreased serum OC by 8.5% and 31.8%, BSAP by 15.8% and 34.6%, and urinary CTx/Cr excretion by 5.6% and 46.5%, respectively, from baseline. In the pooled raloxifene group, the logistic regression relationship between 3-year VF risk and 1-year percentage change for each biochemical marker was statistically significant with PINP (slope estimate = 0.0085, P = 0.009), OC (slope estimate = 0.0068, P = 0.035), and BSAP (slope estimate = 0.0056, P = 0.039), but not with CTx/Cr (slope estimate = 0.0027, P = 0.192). Furthermore, the percent decrease in PINP at 1 year could account for 28% of the total reduction in vertebral fracture risk. In conclusion, a 1-year decrease in PINP, BSAP, or OC, but not CTx/Cr, may be predictive of the 3-year VF risk reduction with raloxifene therapy in this subset of postmenopausal women with osteoporosis.